Geyik Gülcan, Güncüm Enes, Işıklan Nuran
Department of Chemistry, Faculty of Arts and Sciences, Kırıkkale University, Yahşihan, 71450 Kırıkkale, Turkey; Alaca Avni Çelik Vocational School, Hitit University, Çorum, Turkey.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Kırıkkale University, 71450 Yahşihan, Kırıkkale, Turkey.
Int J Biol Macromol. 2023 Oct 1;250:126242. doi: 10.1016/j.ijbiomac.2023.126242. Epub 2023 Aug 8.
Recently, pH-responsive nanogels are playing progressively important roles in cancer treatment. The present study focuses on designing and developing pH-responsive alginate-based nanogels to achieve a controlled release of etoposide (Et) while enhancing its hydrophilicity. Alginate (ALG) is grafted with 2-hydroxypropyl methacrylamide (HPMA) through a microwave-supported method, and the chemical structure of the graft copolymer (ALG-g-PHPMA) was verified by H/C NMR and FTIR techniques. The ALG-g-PHPMA and anticancer drug-loaded ALG-g-PHPMA@Et nanogels were obtained using an emulsion method, and their structures were characterized through FTIR, TG/DSC, AFM/TEM, BET, and DLS analyses. The ALG-g-PHPMA nanogels demonstrated a good drug encapsulation efficiency (79.60 %), displaying a pH-dependent release profile and an in vitro accelerated release of Et compared to the ALG nanogels. Thermal and BET analyses revealed enhanced stability, surface area, and porosity volume of the alginate nanogels. The grafting of PHPMA chains onto alginate altered the surface topology of the ALG nanogels, resulting in lower surface roughness. Furthermore, cytotoxicity tests showed the high biocompatibility of the ALG-g-PHPMA copolymer and its nanogels. The ALG-g-PHPMA@Et nanogels exhibited a higher anticancer effect on lung cancer (H1299) cells than free etoposide. These results suggest that the ALG-g-PHPMA nanogels can be applied as a pH-dependent nanoplatform for delivering anticancer drugs.
近年来，pH响应性纳米凝胶在癌症治疗中发挥着越来越重要的作用。本研究致力于设计和开发基于pH响应性藻酸盐的纳米凝胶，以实现依托泊苷（Et）的控释，同时提高其亲水性。通过微波辅助方法将2-羟丙基甲基丙烯酰胺（HPMA）接枝到藻酸盐（ALG）上，并通过H/C NMR和FTIR技术验证了接枝共聚物（ALG-g-PHPMA）的化学结构。采用乳液法制备了ALG-g-PHPMA和载有抗癌药物的ALG-g-PHPMA@Et纳米凝胶，并通过FTIR、TG/DSC、AFM/TEM、BET和DLS分析对其结构进行了表征。ALG-g-PHPMA纳米凝胶表现出良好的药物包封率（79.60%），呈现出pH依赖性释放曲线，与ALG纳米凝胶相比，Et在体外具有加速释放的特性。热分析和BET分析表明藻酸盐纳米凝胶的稳定性、表面积和孔隙体积有所增强。PHPMA链接枝到藻酸盐上改变了ALG纳米凝胶的表面拓扑结构，导致表面粗糙度降低。此外，细胞毒性测试表明ALG-g-PHPMA共聚物及其纳米凝胶具有高生物相容性。ALG-g-PHPMA@Et纳米凝胶对肺癌（H1299）细胞的抗癌效果比游离依托泊苷更高。这些结果表明，ALG-g-PHPMA纳米凝胶可作为一种pH依赖性纳米平台用于递送抗癌药物。
